Abstract Zikavirus(ZIKV)infectioniscurrentlyanepidemicinthewesternhemisphere.ItisaWHO-declared ?PublicHealthEmergencyofInternationalConcern?sinceFebruary2016duetotheassociationofZIKV infection with microcephaly and other neurologic abnormalities in babies infected in utero and with Guillain-Barresyndromeininfectedadults.AnestimatedfourmillionZIKVinfectionshaveoccurredin the Americas in 2016 and over two billion people live in areas conducive to mosquito-borne transmissionofZIKVworldwide.Todate,autochthonousZIKVinfectionhasbeenreportedinover40 countriesinthewesternhemisphereincludingtheUSprotectorate,PuertoRico,andstateofFlorida. ThereisaclearneedforaccurateandpracticalmethodsofdetectingZIKVinfectionaswellasforthe developmentoftherapeuticagentsandvaccinestocombattheassociateddisease.DetectionofZIKV infectionishampered,however,bythecross-reactivityofanti-ZIKVantibodieswithotherarboviruses present in the same areas including DENV and CHIKV and visa-versa. Specifically, neutralization- based serodiagnostic tests (notably plaque-reduction neutralization tests, PRNT) cannot cleanly distinguish between seropositivity to different members of this set of arboviruses, perhaps because antibodiesdirectedatneutralizingepitopestendtobecross-reactive.Inthisapplicationwepropose an innovative and comprehensive method for discovering targets of non-cross-reactive antibodiestoemergingandestablishedarbovirusesandproposetobeginwithZIKVduetothe internationalpublichealthemergencycreatedbythisvirus.